Abstract 1492: Interaction between Argonaute-2 and Negative Elongation Factor-E in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) continues to be one of the leading cause of cancer-related deaths globally, whose incidence is on the rise in the United States. We and others have shown that high levels of AGO2 is associated with a worse prognosis in HCC patients. Specifically, we showed AGO2 promotes HCC progression by modulating MYC mRNA stability in an RNAi-independent manner. In addition to its canonical role as an RNA binding protein, AGO2 has been demonstrated to regulate gene expression by affecting RNA polymerase II (Pol II) pausing through the Negative Elongation Factor (NELF) complex in Drosophila. It remains elusive how AGO2 modulates the chromatin to affect transcription. Here, we hypothesize AGO2/NELF interactions modulate chromatin accessibility to promote HCC. Immunoprecipitation assays were employed to detect protein-protein interactions between AGO2 and the NELF complex in HCC cells. To determine the effects of AGO2 RNAi-silencing on their interaction, DICER-knockout (via CRISPR) HCC cell lines were also probed for protein-protein interactions. We found AGO2 and NELFE, a member of the NELF complex, interact in both wild-type and DICER-knockout HCC cell lines. These data suggest AGO2 may play an important role in modulating transcription through NELF. Currently, we are investigating the potential interplay between AGO2 and NELFE in modulating chromatin accessibility to promote hepatocarcinogenesis. Understanding the effects of the AGO2/NELF interaction may help elucidate transcriptional regulation in HCC and lead to better therapies for HCC patients. Citation Format: Brittany Natalie Ruiz, Alvaro Lucci, Anna Barry, Kai Zhang, Hien Dang. Interaction between Argonaute-2 and Negative Elongation Factor-E in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1492.